Type 5 acid phosphatase

Abstract

The purple acid phosphatases and uteroferrin belong to a diverse multifunctional class of binuclear ironcontaining proteins that includes haemerythrin and ribonucleotide reductase. In the pig, uteroferrin has been implicated in the delivery of iron to the foetus, but the role of the related human type 5 acid phosphatase that is principally found in resident tissue macrophages is not yet clear. To define further the function of this metalloenzyme, we have isolated and sequenced a cDNA clone for type 5 acid phosphatase and investigated expression of its gene in human tissues. The phosphatase clone contains an open reading frame of 975 bp and encodes a protein of 325 amino acids, including a signal peptide of 19 residues and two potential sites for N-glycosylation. The type 5 acid phosphatase gene mapped to the short arm of human chromosome 19 and was found to have a restriction fragment length polymorphism on digestion with XbaI.Expression of phosphatase mRNA was restricted to mononuclear phagocytes and the enzyme was induced > 20-fold on transformation of normal human monocytes to macrophages by culture in serum-supplemented medium. Type 5 acid phosphatase thus represents a tightly regulated system for the study of molecular events in the differentiation programme of the normal macrophage.Type 5, tartrate-resistant, purple acid phosphatase is a basic, iron-binding protein with high activity towards phosphoproteins, ATP, and 4-nitrophenyl phosphate but with little action on aliphatic phosphates [I, 21. The isoenzyme is found in human alveolar macrophages [3] and osteoclasts [4] and is pathologically increased in Gaucher's cells [5] and in the hairy cells of leukaemic reticuloendotheliosis [6], now known as hairy cell leukaemia. It is thus expressed principally in cells of the human mononuclear macrophage system.Recently the protein has been purified from human and bovine spleen, where it is associated with a particulate fraction [7, 81. lmmunochemical and enzymatic studies [9, 101 as well as protein sequence analysis [I 11 have shown that the splenic enzyme is homologous to uteroferrin, a purple iron-binding protein abundant in the uterine secretions of pregnant sows. Physiological studies in vivo have implicated uteroferrin in the delivery of maternal iron to the developing piglet [12, 131 but the possibility of a similar function for the human tartrateresistant acid phosphatase has not been investigated. However, ultrastructural studies [14] indicate association of the bovine protein with ferritin and haemosiderin aggregates in splenic macrophages, suggesting that it may participate in the Correspondence to

Transcriptional profiling on chromosome 19p indicated frequent downregulation of ACP5 expression in hepatocellular carcinoma

“…25,26 It belongs to the acid phosphatase family that catalyses the conversion of orthophosphoric monoester to alcohol and orthophosphate, and consists of an open reading frame of 975 bp that encodes an iron-containing glycoprotein of 35-37 kDa. [27][28][29] While ACP5 is normally highly expressed in the human liver (NormalTissueAtlas; http://genomewww.stanford.edu/cgi-bin/source/), a phenomenon of acid phosphatase deficiency has been described in HCC tumor cells. 30 Furthermore, ACP5 is considered a useful biomarker for monitoring response to therapy in breast cancer patients with skeletal metastasis.…”

Structure, function, and regulation of tartrate-resistant acid phosphatase

“…In contrast to most plants studied, Southern blot experiments on human, 76 pig, 74 and mouse 19 have detected a single gene, and no related sequences exist in any mammalian EST databases. The human TRAP gene is located on chromosome 19 (19p13.2-13.3) 70,76 and in the syntenic region on mouse chromosome 9.…”

“…The human TRAP gene is located on chromosome 19 (19p13.2-13.3) 70,76 and in the syntenic region on mouse chromosome 9. 38 The overall intron-exon structure of the mouse and human TRAP genes is conserved; they contain five exons with the ATG ("start") codon at the beginning of exon 2.…”

Osteoclastic Tartrate-resistant Acid Phosphatase (Acp 5): Its Localization to Dendritic Cells and Diverse Murine Tissues

“…The human TRAP cDNA, 1359 bp isolated from human spleen (Lord et al 1990) was cloned into the Eco RI site of pGEM-7Zf( ϩ ). 35 S-labeled riboprobes were prepared from linearized templates which were transcribed from T7 or SP6 promotors of the pGEM vector to generate antisense and sense probes.…”

“…Although the human gene maps to chromosome 19 and contains a putative N-terminal lysosomal leader sequence (Lord et al 1990), the cognate protein is secreted into the resorptive vacuole beneath the ruffled border of the osteoclast during bone resorption (Reinholt et al 1990). Lately, evidence has been presented that TRAP is not secreted into the ruffled border but rather is present in vesicles that are fused to transcytotic vesicles.…”